Preparation method of kung-fu acid

Abstract

The invention relates to the field of organic synthesis, and particularly discloses a preparation method of kung-fu acid. Comprising the following steps: carrying out an addition reaction on 3-methyl-1-butene and 1, 1, 1-trichlorotrifluoroethane under the action of a catalyst to obtain 2, 2, 4-trichloro-1, 1, 1-trifluoro-5-methylhexane, carrying out an elimination reaction under a strong alkaline condition to obtain 2-chloro-1, 1, 1-trifluoro-5-methyl-2, 4-hexadiene, carrying out a '1 + 2' cycloaddition reaction on the 2-chloro-1, 1, 1-trifluoro-5-methyl-2, 4-hexadiene and a phosphorus ylide reagent to obtain 2-chloro-1, 1, 1-trifluoro-5-methyl-2, 4-hexadiene. And finally, saponifying and acidifying the kung-fu acid methyl ester to obtain the product kung-fu acid. The process is simple to operate, the raw materials are cheap and easy to obtain, the solvent can be recycled, the conversion rate is high, impurities are few, and the method is more suitable for industrial production.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and more specifically, to a method for preparing kinematic acid. Background Technology

[0002] Pyrethroids are an important class of insecticides, characterized by high efficiency, broad spectrum, low toxicity, and biodegradability. They are widely used in agricultural and sanitary pest control, and to date, more than 50 varieties of pyrethroids have been commercialized, with sales increasing year by year. Kungfu acid, also known as monochlorotrifluoroacetic acid, with the chemical name 3-(2-chloro-3,3,3-trichloropropen-1-yl)-2,2-dimethylcyclopropanecarboxylic acid, is a common intermediate used in the synthesis of several pyrethroids. It can be used to synthesize a series of products such as permethrin, methamidophos, cypermethrin, deltamethrin, fenvalerate, cypermethrin, and heptafluthrin. The chemical structural formula of kungfu acid is: .

[0003] The mainstream preparation method for kung fu acid is as follows: using methyl benzoate as the starting material, an addition reaction is carried out with 1,1,1-trichlorotrifluoroethane (F113a) in the presence of a catalyst (usually cuprous chloride and ethanolamine). The adduct undergoes intramolecular cyclization under the action of a strong base, followed by saponification, eliminating chlorine atoms in the process. Finally, acidification yields kung fu acid. Methyl benzoate is relatively expensive, accounting for approximately 60% of the material cost, resulting in high costs and low profit margins for this preparation method. Summary of the Invention

[0004] In view of the shortcomings of the existing technology, and in order to reduce material costs and improve economic efficiency, this application provides a method for preparing kung fu acid.

[0005] The preparation method of kung fu acid provided in this application adopts the following technical solution: A method for preparing kinematic acid, the synthetic route is as follows:

[0006] Includes the following steps: (1) Compound 2 is 3-methyl-1-butene, which undergoes an addition reaction with 1,1,1-trichlorotrifluoroethane under the action of a catalyst to give adduct 3, which is 2,2,4-trichloro-1,1,1-trifluoro-5-methylhexane.

[0007] (2) Under strongly alkaline conditions, adduct 3 undergoes an elimination reaction to give eliminator 4, which is 2-chloro-1,1,1-trifluoro-5-methyl-2,4-hexadiene.

[0008] (3) Eliminator 4 undergoes a “1+2” cycloaddition reaction with reagent 5, namely phosphorus ylide reagent, to obtain cyclopolymer 6, which is methyl phosphonate.

[0009] (4) Cyclomeric compound 6 is saponified and acidified to obtain compound 1, namely the product kung fu acid.

[0010] Optionally, the catalyst in step (1) is cuprous chloride and ethanolamine, and the reaction solvent is tert-butanol.

[0011] Optionally, the strongly alkaline condition in step (2) is sodium hydroxide or potassium hydroxide, preferably sodium hydroxide, and the reaction solvent is tert-butanol or toluene, preferably tert-butanol.

[0012] Optionally, the reaction solvent used in step (3) is tetrahydrofuran or toluene, preferably toluene.

[0013] Optionally, the reaction solvent used in step (4) is water.

[0014] In summary, the method for preparing kung fu acid in this application uses inexpensive and readily available 3-methyl-1-butene instead of the more expensive methyl benzoate, and the phosphorus ylide reagent can be prepared from methyl chloroacetate and triphenylphosphine, further reducing raw material costs. Other raw materials used are also common and inexpensive chemical raw materials. The entire process is simple to operate, uses inexpensive and readily available raw materials, and the solvents can be recycled and reused. It boasts high conversion rates and low impurities, making it more suitable for industrial production. Detailed Implementation

[0015] The present application will be further described in detail below with reference to the embodiments. Preparation Example 1

[0016] Preparation of reagent 5, phosphorus ylide reagent: 2106 g (8.0 mol) of triphenylphosphine or recovered triphenylphosphine was dissolved in 8.5 L of toluene, and 911 g (8.4 mol) of methyl chloroacetate was added dropwise at 22.5 ± 2.5 °C. With stirring, a large amount of white solid gradually precipitated. After filtration, the phosphonium salt was washed with 2 L of toluene and redispersed in 8.5 L of toluene. 768 g of sodium tert-butoxide (8.0 mol) was slowly added at 2.5 ± 2.5 °C. The solution quickly turned blood red, yielding the toluene solution of phosphorus ylide reagent. The solution was stored at low temperature for use in cycloaddition reactions. Example Example 1

[0017] A method for preparing kinematic acid includes the following steps: (1) Add 5 L of tert-butanol, 20 g of ethanolamine, and 20 g of cuprous chloride to the reactor, then introduce 721 g (10.3 mol) of 3-methyl-1-butene (compound 2), raise the temperature, and when the temperature inside the reactor reaches reflux, start adding 1870 g (10 mol) of 1,1,1-trichlorotrifluoroethane dropwise. After the addition is complete, maintain the reflux reaction for 15 ± 3 h. After the reaction is complete, transfer the material to a settling tank, let it stand, and allow the cuprous chloride to settle to the bottom of the tank. Separate the supernatant, which is adduct 3, and adduct 3 is 2,2,4-trichloro-1,1,1-trifluoro-5-methylhexane.

[0018] (2) Add 2000g (50mol) sodium hydroxide to the whole batch of adduct 3, seal the system, heat to 125±5℃, and react for 27.5±2.5h. Distill to recover tert-butanol, and distill to obtain 1348g of eliminator 4, which is 2-chloro-1,1,1-trifluoro-5-methyl-2,4-hexadiene, a pale yellow liquid.

[0019] The yield of the above two steps was 73%.

[0020] (3) Dissolve the entire batch of eliminator 4 (1348g, 7.3mol) in 5.4L of toluene, add the entire batch of reagent 5 phosphorus ylide reagent prepared in Example 1 in toluene, reflux for about 4h, and a “1+2” cycloaddition reaction occurs to obtain cyclopolymer 6, which is methyl benzoate.

[0021] (4) After the reaction in step (3) is completed, add 1300g of 6N sodium hydroxide aqueous solution to carry out the saponification reaction at 55±5℃ for 2.5±0.5h. Let stand for separation, distill the organic layer to recover toluene, and the residue in the reactor is triphenylphosphine, which is recycled for the preparation of phosphorus ylide reagent. Acidify the aqueous layer with hydrochloric acid dropwise, adjust the pH to 2.8±0.2, and filter. Add about 7.5L of water to the filter cake and reflux to make a pulp, centrifuge, and dry to obtain 1524g of compound 1, namely kungfu acid, which is a white powder with a yield of 86% (based on elimination product 4) and an overall yield of 63% (based on 1,1,1-trichlorotrifluoroethane). Example 2

[0022] A method for preparing kinematic acid includes the following steps: (1) Add 5 L of tert-butanol, 20 g of ethanolamine, and 20 g of cuprous chloride to the reactor, then introduce 721 g (10.3 mol) of 3-methyl-1-butene (compound 2), raise the temperature, and when the temperature inside the reactor reaches reflux, start adding 1870 g (10 mol) of 1,1,1-trichlorotrifluoroethane dropwise. After the addition is complete, maintain the reflux reaction for 15 ± 3 h. After the reaction is complete, transfer the material to a settling tank, let it stand, and allow the cuprous chloride to settle to the bottom of the tank. Separate the supernatant, which is adduct 3, and adduct 3 is 2,2,4-trichloro-1,1,1-trifluoro-5-methylhexane.

[0023] (2) Add 2800g (50mol) of potassium hydroxide to the whole batch of adduct 3, seal the system, heat to 125±5℃, and react for 27.5±2.5h. Distill to recover tert-butanol, and distill to obtain 1366g of eliminator 4, which is 2-chloro-1,1,1-trifluoro-5-methyl-2,4-hexadiene, a pale yellow liquid.

[0024] The yield of the above two steps was 74%.

[0025] (3) Dissolve the entire batch of eliminator 4 (1366g, 7.4mol) in 5.4L of toluene, add the entire batch of reagent 5 phosphorus ylide reagent prepared in Example 1 in toluene, reflux for about 4h, and a “1+2” cycloaddition reaction occurs to obtain cyclopolymer 6, which is methyl methacrylate.

[0026] (4) After the reaction in step (3) is completed, add 1300g of 6N sodium hydroxide aqueous solution to carry out the saponification reaction at 55±5℃ for 2.5±0.5h. Let stand for separation, distill the organic layer to recover toluene, and the residue in the reactor is triphenylphosphine, which is recycled for the preparation of phosphorus ylide reagent. Acidify the aqueous layer with hydrochloric acid dropwise, adjust the pH to 2.8±0.2, and filter. Add about 7.5L of water to the filter cake and reflux to make a pulp, centrifuge, and dry to obtain 1526g of compound 1, namely kungfu acid, which is a white powder with a yield of 85% (based on elimination product 4) and an overall yield of 63% (based on 1,1,1-trichlorotrifluoroethane). Example 3

[0027] A method for preparing kinematic acid includes the following steps: (1) Add 5 L of tert-butanol, 20 g of ethanolamine, and 20 g of cuprous chloride to the reactor, then introduce 721 g (10.3 mol) of 3-methyl-1-butene (compound 2), raise the temperature, and when the temperature inside the reactor reaches reflux, start adding 1870 g (10 mol) of 1,1,1-trichlorotrifluoroethane dropwise. After the addition is complete, maintain the reflux reaction for 15 ± 3 h. After the reaction is complete, transfer the material to a settling tank, let it stand, and allow the cuprous chloride to settle to the bottom of the tank. Separate the supernatant, which is adduct 3, and adduct 3 is 2,2,4-trichloro-1,1,1-trifluoro-5-methylhexane.

[0028] (2) Add 2000g (50mol) sodium hydroxide to the whole batch of adduct 3, seal the system, heat to 125±5℃, and react for 27.5±2.5h. Distill to recover tert-butanol, and distill to obtain 1385g of eliminator 4, which is 2-chloro-1,1,1-trifluoro-5-methyl-2,4-hexadiene, a pale yellow liquid.

[0029] The yield of the above two steps is 75%.

[0030] (3) Dissolve the entire batch of eliminator 4 (1385g, 7.5mol) in 5.4L of tetrahydrofuran, add the entire batch of reagent 5 phosphorus ylide reagent prepared in Preparation Example 1 in toluene solution, and a "1+2" ​​cycloaddition reaction occurs. The reaction is closed and heated to 113±2℃ for about 4h to obtain cyclopolymer 6, which is methyl methacrylate.

[0031] (4) After the reaction in step (3) is completed, add 1300g of 6N sodium hydroxide aqueous solution to carry out the saponification reaction at 55±5℃ for 2.5±0.5h. Let stand and separate the layers. Distill the organic layer to recover the solvent. The residue in the reactor is triphenylphosphine, which is recycled for the preparation of phosphorus ylide reagent. Add hydrochloric acid dropwise to the aqueous layer to acidify and adjust the pH to 2.8±0.2. Filter. Add about 7.5L of water to the filter cake and reflux to make a pulp. Centrifuge and dry to obtain 1383g of compound 1, namely kung fu acid, which is a white powder with a yield of 76% (based on elimination product 4) and an overall yield of 57% (based on 1,1,1-trichlorotrifluoroethane). Comparative Example 1

[0032] A method for preparing kinematic acid includes the following steps: (1) Additive 680g of methyl benzoate was pumped into the addition reactor, followed by 1000g of 1,1,1-trichlorotrifluoroethane, 600g of tert-butanol, 32g of ethanolamine catalyst, and 13g of cuprous chloride. The temperature was slowly raised to 85℃ and held for 10 hours. Low-boiling-point components were removed at 120℃ under normal pressure. The mixture was then cooled to 60℃ and discharged, allowing it to precipitate for 8 hours. The clarified liquid was pumped into a desolventizing reactor, heated to 140℃, and subjected to vacuum distillation to remove high-boiling-point components. Samples were taken for analysis, and the methyl benzoate content was controlled to be ≤1% for compliance. The mixture was then cooled and discharged, allowing it to precipitate for 8 hours. The tar was then removed, yielding adduct 8, with a yield of 1290g.

[0033] (2) Ring closure Add 900g of tert-butanol and 380g of DMF to the cyclization reactor, cool to -15℃, add 170g of sodium tert-butoxide, and then add 430g of the adduct dropwise, maintaining the addition temperature at -15~-5℃. After the addition is complete, take a sample for analysis; the adduct content should be less than 1% to be considered acceptable. Heat to 90℃ and desolvate under reduced pressure to remove tert-butanol and DMF. Add 1000g of water, stir for 30 minutes, let stand for 30 minutes, and allow the layers to separate. Slowly heat the organic layer to 145℃ and distill under reduced pressure to obtain cyclizer 9.

[0034] (3) Saponification Add 1350g methanol, 720g sodium hydroxide, and 950g water to the entire batch of cyclized compound. Heat to 80-85℃ and reflux for 8 hours. Add 240g sodium hydroxide and 300g water. Reflux for another 8 hours, then add 120g sodium hydroxide and 150g water. After the reaction is complete, remove methanol to 95℃, cool, discharge, and filter.

[0035] (4) Acidification Add 10% dilute hydrochloric acid dropwise to the entire batch of saponification filtrate to adjust the pH value to 2.5±0.5, centrifuge, dry, and obtain 591g of kung fu acid, with a yield of 51% (based on methyl benzoate).

[0036] The specific synthetic route is as follows:

[0037] As can be seen from Examples 1, 2, and 3 and Comparative Example 1, the yield of kungfu acid obtained by the preparation methods of each example of this application is higher than that of Comparative Example 1. Furthermore, in the method for preparing kungfu acid in this application, inexpensive and readily available 3-methyl-1-butene is used instead of the more expensive methyl benzoate, and the phosphorus ylide reagent can be prepared from triphenylphosphine and methyl chloroacetate obtained during the preparation process, further saving raw material costs. Other raw materials used are also common and inexpensive chemical raw materials. The entire process is simple to operate, the raw materials are inexpensive and readily available, the solvents can be recycled and reused, the conversion rate is high, and the impurities are few, making it more suitable for industrial production.

[0038] The above-described embodiments are merely explanations of the present invention and are not intended to limit the present invention. After reading this specification, those skilled in the art can make modifications to these embodiments without contributing any inventive step, but such modifications are protected by patent law as long as they are within the scope of the claims of the present invention.

Claims

1. A method for preparing kinematic acid, characterized in that, Includes the following steps: (1) 3-Methyl-1-butene undergoes an addition reaction with 1,1,1-trichlorotrifluoroethane under the action of a catalyst to give adduct 3, which is 2,2,4-trichloro-1,1,1-trifluoro-5-methylhexane; (2) Under strongly alkaline conditions, adduct 3 undergoes an elimination reaction to give eliminator 4, which is 2-chloro-1,1,1-trifluoro-5-methyl-2,4-hexadiene; (3) Eliminator 4 undergoes a "1+2" ​​cycloaddition reaction with reagent 5, i.e., phosphorus ylide reagent, to give cyclized compound 6, which is methyl fumonisin; (4) Cyclomeric compound 6 is saponified and acidified to obtain compound 1, namely the product kung fu acid.

2. The method for preparing kung fu acid according to claim 1, characterized in that, The catalysts in step (1) are cuprous chloride and ethanolamine, and the reaction solvent is tert-butanol.

3. The method for preparing kung fu acid according to claim 1, characterized in that, The strong alkaline condition mentioned in step (2) is sodium hydroxide or potassium hydroxide, and the reaction solvent is tert-butanol or toluene.

4. The method for preparing kung fu acid according to claim 1, characterized in that, The reaction solvent used in step (3) is tetrahydrofuran or toluene.

5. The method for preparing kung fu acid according to claim 1, characterized in that, The reaction solvent used in step (4) is water.

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